Barcelona hold an eight-point lead over second-placed Atletico, which would be reduced to five if the visitors can win at the Nou Camp.
Atletico, however, have never beaten the Catalans in the top flight since Simeone took charge in December 2011.
"That we've never won at the Nou Camp (actually) makes me very optimistic," Simeone told reporters on Friday.
"If we win tomorrow and then we don't win the next games, it counts for nothing. Tomorrow we have to show the identity which this team has."
After Atletico were knocked out of the Champions League by Juventus in the last 16, their hopes of glory this season are pinned on winning La Liga.
Barcelona are fighting for the treble but coach Ernesto Valverde is not taking anything for granted.
Valverde says even if his team beat Atletico, extending their lead to 11 points with seven matches remaining, the title race will not be over.
"Many people said La Liga was over in January and later, when you don't win, and your rivals do, the title race is back on," Valverde told a news conference.
"While the mathematics don't say (it's over), you have to keep going until the end."
Valverde says he wants to maintain the team's usual style, even up against an abrasive side like Atletico.
"We will try to stay faithful to our game," added the coach.
"The three points are very important to both teams, in our case to extend our advantage and for them to cut the gap. Mathematically the distance is not definitive."
(Reporting by Rik Sharma; Editing by Toby Davis)
